Detection of vimentin specific autoreactive CD8+T cells in cardiac transplant patients

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Evidence is emerging that autoimmunity plays a role in allograft rejection. We previously reported that presence of autoreactive antibodies to the non-polymorphic self-protein vimentin in cardiac transplant patients. The objective of the present study was to seek evidence of vimentin-specific self-MHC restricted CD8+ T cells. Two peptide sequences from vimentin that bound HLA-A∗0201 were identified and fluorochrome labelled A∗0201 tetramers with each peptide constructed to screen for vimentin specific T cells. Six cardiac transplant patients were selected on the basis of being A∗0201 positive and having high titres of anti-vimentin antibodies, all were 3–6 years post transplant at the time of testing. Peripheral blood lymphocytes (PBL) were tested for binding to the TAP deficient cell line T2, either alone (and not presenting peptides) or loaded with one of two relevant nine amino acid peptides derived from vimentin (abbreviated to SLQ and LLQ). PBL from six A∗0201 positive heart transplant patients did not bind the vimentin tetramers. However, after 21 days in vitro culture with weekly peptide stimulation, tetramer binding CD8+ Tcells were detected in two patients. In one patient, 2.1% and 4.5% of PBL bound T2/SLQ and T2/LLQ respectively, in the other patient 9.4% of PBL bound T2/LLQ. Less than 0.02% PBL bound to unloaded T2 cells.